Hand-foot skin reaction (HFSR) and overall survival (OS) in the phase 3 RESORCE trial of regorafenib for treatment of hepatocellular carcinoma (HCC) progressing on sorafenib

Background: Skin toxicity is a known adverse effect of multikinase inhibitors, and was shown to be a predictor of OS in patients (pts) with HCC treated with sorafenib (Reig M, 2014). In the RESORCE trial, regorafenib improved OS versus placebo in pts with HCC progressing on sorafenib (HR 0.62, 95% CI 0.50, 0.78; Bruix J, 2017). This retrospective analysis explored whether HFSR with regorafenib was associated with OS in RESORCE. Methods: Pts in RESORCE who were randomized to regorafenib 160 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether or not they had HFSR. Estimates of OS (95% CI) were calculated using the Kaplan-Meier method. Pts who were randomized, but not treated, were included in the no HFSR group for the analysis of survival. Results: Of 379 pts randomized, 374 received at least one dose of regorafenib. Of the treated pts, 53% (n = 199) had HFSR of any grade and 13% (n = 47) had grade 3 HFSR. Among pts with HFSR at any time during the study, 77% (n = 153) had the first HFSR event (any grade) during Cycle 1. Subgroups of pts with and without HFSR at any time had some imbalances in baseline characteristics (Table). OS was improved in pts who had HFSR at any time versus those who did not (Table). Pts who had a HFSR event during Cycle 1 also had improved OS versus those who did not (median OS 13.2 vs. 8.5 months; HR 0.66, 95% CI 0.51, 0.86). Tab. 1: HFSR and OS HFSR (any grade: n = 199) No HFSR (n = 180) Median age, yrs (range) 61 (21 – 84) 65 (19 – 85) Geographic region Asia/rest of world, % 50/50 24/76 ECOG performance status 0/1, % 75/25 54/46 BCLC stage A/B/C, % 1/17/83 0/11/89 AFP >/= 400 ng/ml, % 40 46 MVI and/or EHD, % 77 83 Child-Pugh score 5/6/7, % 76/22/2 51/47/1 Median OS, months (95% CI) 14.1 (11.7; 16.5) 6.6 (5.0; 8.5) Hazard Ratio (95% CI) 0.52 (0.40; 0.67) Conclusions: In this post-hoc exploratory analysis, HFSR with regorafenib was associated with improved OS, as was previously shown for sorafenib. The potential confounding influence of baseline factors requires further investigation. Clinical trial information: NCT01774344.